ObjectiveTo investigate the therapeutic mechanism of Xuefu Zhuyutang （XFZYT） for metabolic-associated fatty liver disease （MAFLD） through integrated network pharmacology and animal experiments. MethodsNetwork pharmacology was utilized to predict the core components， key therapeutic targets， and signaling pathways of XFZYT in the treatment of MAFLD. For animal experiments， a rat model of MAFLD was established by feeding a high-cholesterol diet for 4 weeks. Intervention was then administered with low-dose （2 g·kg^-1） and high-dose （4 g·kg^-1） XFZYT for 2 weeks. Biochemical assays were performed to measure the serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. In addition， the activities of superoxide dismutase （SOD） and catalase （CAT） and levels of malondialdehyde （MDA） and glutathione （GSH） in the serum were measured. The same way was adopted to measure the levels of TC and TG in the liver tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to quantify the serum levels of interleukin （IL）-6， IL-1β， and tumor necrosis factor-alpha （TNF-α）. Histopathological evaluations included hematoxylin and eosin （HE） staining for liver tissue morphology， Oil Red O staining for lipid deposition， and dihydroethidium （DHE） probe staining for reactive oxygen species （ROS） levels. Western blot analysis was conducted to assess the protein levels of AMP-activated protein kinase （AMPK）， phosphorylated （p）-AMPK， nuclear factor erythroid 2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， nuclear factor-kappa B （NF-κB）， and p-NF-κB in the liver tissue. Untargeted metabolomics analysis of the serum was performed by liquid chromatography-tandem mass spectrometry （LC-MS/MS）. ResultsNetwork pharmacology analysis predicted 155 potential targets of XFZYT for MAFLD treatment， with core targets including signal transducer and activator of transcription 3 （STAT3）， protein kinase B1 （Akt1）， TNF， and IL-6. Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment primarily implicated the AMPK signaling pathway. Animal experiments demonstrated that compared with the normal group， the model group exhibited dyslipidemia， hepatic function impairment， pronounced hepatic lipid deposition， and inflammatory manifestations， with elevated serum levels of AST， ALT， TC， TG， LDL， and MDA （P<0.05）， reduced HDL and GSH levels plus decreased SOD and CAT activities （P<0.05）， downregulated protein levels of Nrf2， HO-1， and p-AMPK （P<0.05）， and upregulated protein level of p-NF-κB （P<0.05） in the liver tissue. Compared with the model group， XFZYT intervention groups showed significant amelioration of dyslipidemia and hepatic function impairment， markedly reduced hepatic lipid deposition and inflammatory cell infiltration， decreased serum levels of AST， ALT， TC， TG， LDL， and MDA （P<0.05）， increased HDL and GSH levels plus enhanced SOD and CAT activities （P<0.05）， upregulated protein levels of Nrf2， HO-1， and p-AMPK （P<0.05）， and downregulated protein level of p-NF-κB （P<0.05）. Serum metabolomics revealed 511 differentially expressed metabolites （231 upregulated and 280 downregulated） between normal and model groups， while XFZYT groups versus model group showed 94 differential metabolites （51 upregulated and 43 downregulated）. Among them， 11 metabolites displayed the most significant alterations， with enriched pathways including glycerolipid metabolism， cholesterol metabolism， and insulin resistance， multiple of which demonstrated AMPK association. ConclusionXFZYT alleviates MAFLD by regulating the AMPK signaling pathway and associated metabolic networks.

BACKGROUND:Mechanical factors can affect the angiogenic ability of vascular endothelial cells.How the vessel number affects the hydrodynamic properties of microvessels remains to be clarified. OBJECTIVE:To investigate the influence of vessel number on the hydrodynamics of vascular networks based on computational fluid dynamics. METHODS:Three three-dimensional models of vascular network with different vessel numbers were constructed using the Geometry module of ANSYS 19.0 software,and then the vascular network was meshed to tetrahedral elements in Mesh module.The vascular network was assumed to rigid wall without slip,and the blood was assumed to laminar,viscous,and incompressible Newtonian fluid.Blood density,velocity,and a series of blood viscosity coefficients were also established.The Navier-Stokes equation was used for calculation.Hydrodynamic properties of different parts of vascular network with different vessel numbers were analyzed and compared. RESULTS AND CONCLUSION:The streamline,velocity,and mass flow all had the same trend in the vascular network,that is,the outlet and inlet were higher and the middle junction of vascular network was lower.The more the number of vessels,the thinner the blood flow lines in each part of the vascular network.Also,the velocity,mass flow,and wall shear decreased with the increase of the number of blood vessels.Therefore,the changes in vessel number could influence the hydrodynamic environment in the vascular network.Computational fluid dynamics indicates that the changes in vessel numbers can influence the hydrodynamic properties of blood,and provides a new idea for treating bone hypoperfusion-induced diseases(fracture nonunion,bone defect,osteoporosis,etc.)through tonifying kidney and activating blood circulation based on the coupling between angiogenesis and osteogenesis.

Objective To investigate the expression of CKS1B in endometrial carcinoma(EC)and its relationship with clinicopathological features and prognosis.Methods The expression profile data and clinical data of CKS1B from the TCGA and GTEx databases were downloaded to investigate the expression of CKS1B in EC and its relationship with clinicopathological features.The expression of CKS1B at the protein level was verified using the UALCAN database.The relationship between CKS1B expression and clinicopathological parameters was analyzed by Logistic regression.The r program perform enrichment analysis on CKS1B co-expressed genes in the TCGA database.Finally,CKS1B mRNA expression was discovered in the cell lines Ishikawa and HEC-1-A by quantitative real-time PCR(qRT-PCR).CKS1B protein expression was detected in EC tissues and adjacent tissues by Western Bolt(WB).Results CKS1B mRNA and protein were remarkably higher in EC tissues than in normal endometrium,and the differences were statistically significant(P<0.05).The level of CKS1B mRNA expression was strongly correlated with FIGO stage(F=42.994),histological grade(F=70.350),histological type(F=87.341)and age(F=40.097)(all P<0.05).The results of the Kaplan-Meier method showed that patients with high CKS1B mRNA expression had a lower overall survival rate(Log-rank x2=1.175,P<0.01).Multifactorial COX analysis showed that FIGO stage(HR=3.065,95%CI:1.906～4.926)and CKS1B expression(HR=1.856,95%CI:1.154～2.985)were independent risk factors affecting the prognosis of patients with EC(P<0.05).GO analysis showed that CKS1B was mainly involved in nuclear division and chromosome separation.KEGG analysis showed it was mainly enriched in the cell cycle,spliceosome and DNA replication.Further verification showed that CKS1B mRNA was highly expressed in Ishikawa and HEC-1-A cell lines(F=44.560,P<0.001),CKS1B protein was highly expressed in EC tissues(t=14.900,P<0.001).Conclusion CKS1B is upregulated in EC and is linked to clinicopathological variables in the patients.It may play a role in the development of EC by regulating the cell cycle,and it is expected to be a new marker for the diagnosis and prognosis of EC.

Objective:To investigate the clinical phenotype and genetic characteristics of patients with Fabry disease caused by a GLA variant, IVS4+919G>A.Methods:It was a prospective study. Fabry disease screening was conducted among high-risk population in Ninghai from October 2021 to August 2023. Those children with decreased α-galactosidase enzyme activity<2.40 μmol/(L·h) or elavated Lyso-GL-3 level>1.10 μg/L in dried blood spot (DBS) method underwent GLA genetic testing for diagnosis confirmation. Meanwhile, family screening was carried out. A proband and his family members diagnosed with Fabry disease were research subjects. The clinical and genetic characteristics of patients with Fabry disease caused by the GLA variant (IVS4+919G>A) were analyzed.Results:The female proband aged 9.8 years with pain in both lower limbs as the initial symptom was found to have a heterozygous GLA variant IVS4+919G>A among 102 patients. In family screening, there were 4 family members (proband's father, elder sister, elder male cousin and elder female cousin) with Fabry disease and a family member (proband's fifth aunt) with a GLA variant. Among these 4 diagnosed family members, the elder male cousin of the proband, a boy aged 13.2 years had a heterozygous GLA variant, IVS4+919G>A with intermittent pain in both lower limbs as the initial symptom. The proband′s father had knee joint pain. The proband′s elder sister had decreased vision and his elder female cousin had no obvious symptoms. The proband′s fifth aunt with a GLA variant had decreased vision.Conclusions:High-risk screening in children and family screening are helpful for early diagnosis and treatment of Fabry disease. Neuropathic pain may be a early symptom in children with Fabry disease caused by the GLA variant, IVS4+919G>A.

AIM:To investigate the effect of paeoniflorin(PF)on TLR4/MyD88 signaling pathway in liver of rats with metabolic dysfunction-associated fatty liver disease.METHODS:SPF grade male SD rats were randomly divid-ed into four groups:normal control(NC)group,model control(MC)group,low-dose paeoniflorin(PL)group,and high-dose paeoniflorin(PH)group.The normal group was given standard diet,and the other three groups were given high-fat diet for 8 weeks.From the fifth week,rats in paeoniflorin groups were given low dose(25 mg·kg-1·d-1)or high dose(50 mg·kg-1·d-1)paeoniflorin for 4 weeks.Serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC)and triglyceride(TG)were measured by biochemical method.The levels of tumor necrosis factor(TNF)-α was detected by ELISA.Pathological change of the liver was detected with hematoxylin-eosin(HE)staining and oil red O staining,and evaluated semi-quantitatively with the nonalcoholic fatty liver disease activity score(NAS).The expres-sion levels of TLR4,MyD88 and phosphorylated nuclear factor(p-NF)-κB p65 in liver tissues were detected by immuno-histochemistry and Western blot.RESULTS:Compared with the NC group,rats in the MC group showed increased TC,TG,ALT,AST and TNF-α in serum(P<0.05),and more lipid droplets in hepatocytes and inflammatory cell infiltration in the portal area,with higher NAS,TLR4,MyD88 and p-NF-κB p65 proteins in liver tissue(P<0.05).However,pae-oniflorin could reduce TC,TG,ALT,AST and TNF-α in serum(P<0.05),improve histopathological changes of liver,decrease the NAS scoring(P<0.05),and inhibit hepatic TLR4/MyD88/p-NF-κB p65 expressions(P<0.05).CONCLU-SION:Paeoniflorin could improve the lipid metabolism disorder and reduce liver inflammation during MAFLD,and the latter effect might be in part related to the inhibition of TLR4/MyD88 signaling pathway.

Objective:To explore the value of subspecialty group collaboration combined with disease checklist-driven learning in overcoming the impact of the specialized disease treatment mode in subspecialty establishment on the cultivation of professional postgraduate students.Methods:In the teaching of general surgery and gastroenterology, sixty professional postgraduate students of grade 2019 were randomly divided into control group and experimental group, with 30 students in each group. The control group received traditional teaching, while the experimental group received the teaching mode of subspecialty group collaboration combined with disease checklist-driven learning. The teaching effectiveness and the degree of satisfaction with teaching were compared between the two groups. The data were analyzed using the t test and the chi-squared test using SPSS 20.0. Results:In actual teaching, compared with the control group, the experimental group showed significantly higher scores of theoretical assessment (71.51±11.32 vs. 87.23±10.51, P<0.05) and case analysis (73.61±6.82 vs. 92.37±6.87, P<0.05). The rates of satisfaction with theoretical knowledge learning, application of clinical thinking ability for diseases, teaching organization forms, and teaching effectiveness were 90.00%(27/30), 86.67%(26/30), 96.67%(29/30), and 93.33%(28/30) in the experimental group, respectively, which were significantly higher than those of the control group [40.00%(12/30), 23.33%(7/30), 40.00%(12/30), and 46.67%(14/30), respectively; all P<0.05]. Conclusions:The subspecialty group collaboration combined with disease checklist-driven learning mode can overcome the problems of "narrow disease spectrum and narrow knowledge scope" in specialized postgraduate education, and guide students to break the teaching barriers generated by subspecialty construction to create a new form of comprehensive and multi-disease learning, with good prospects for promotion and application.

Objective:To investigate the effects and significance of acute and chronic trauma on brain degree centrality (DC) in patients with post-traumatic stress disorder (PTSD) who lost their only child at resting state.Methods:Retrospectively, the study enrolled a total of 51 parents with PTSD, including 35 PTSD parents whose children was lost in emergencies (acute bereaved PTSD group) and 16 PTSD parents whose children was lost of chronic causes such as diseases (chronic bereaved PTSD group). Fifty local adults were also included as healthy controls (HC group). The clinical administered PTSD scale(CAPS) was used to evaluate the severity of the subjects' clinical symptoms.Resting-state functional magnetic resonance imaging(fMRI) data of all subjects were collected and DC values were calculated.SPSS 22.0 software was used for statistical analysis.Covariance analysis was performed among three groups, while post hoc was performed between any two groups.What's more, correlation analyses were utilized between abnormal brain regions and the scores of CAPS.Results:Significant group effects were found in multiple regions, including the right inferior temporal gyrus (MNI: x, y, z=66, -27, -21), right temporal pole (MNI: x, y, z=54, 15, -9), right orbital inferior frontal gyrus (MNI: x, y, z=42, 21, -15), bilateral medial superior frontal gyri (MNI: right x, y, z=6, 63, 12; left x, y, z=-3, 60, 18), left inferior parietal angular gyrus (MNI: x, y, z=-45, -36, 51) and left postcentral gyrus (MNI: x, y, z=-45, -33, 51). Compared with HC group, the DC of two patient groups increased in the right inferior temporal gyrus (MNI: acute x, y, z=63, -27, -21; chronic x, y, z=63, -21, -27); the DC of acute bereaved PTSD group decreased in the right temporal pole (MNI: x, y, z=45, 21, -15) and the right orbital inferior frontal gyrus (MNI: x, y, z=48, 24, -12), while the DC of chronic bereaved PTSD group decreased in the left inferior parietal angular gyrus (MNI: x, y, z=-45, -36, 51) and left postcentral gyrus (MNI: x, y, z=-45, -33, 51). Compared with chronic bereaved PTSD group, the DC of acute bereaved PTSD group increased in the left inferior parietal angular gyrus (MNI: x, y, z=-33, -39, 42) and left postcentral gyrus (MNI: x, y, z=-45, -33, 51), while decreased in the right temporal pole (MNI: x, y, z=51, 12, -9), right orbital inferior frontal gyrus (MNI: x, y, z=42, 21, -15) and bilateral medial superior frontal gyri (MNI: left x, y, z=0, 57, 15; right x, y, z=3, 57, 15). In chronic bereaved PTSD group, the DC of the left postcentral gyrus was negatively correlated with C1 (avoid trauma-related thoughts, feelings) score in CAPS ( r=-0.606, P=0.028). In acute bereaved PTSD group, the DC of the left medial superior frontal gyrus was negatively correlated with D4 (high vigilance) score ( r=-0.416, P=0.020). Conclusion:There exist functional abnormalities of multiple brain regions in acute and chronic bereaved parents with PTSD.The high arousal symptoms of the former may be related with the abnormalities of prefrontal-amygdala neural circuit, while the latter show higher avoidance which may be associated with the dysfunction of somatosensory brain regions such as postcentral gyrus.

Objective:To investigate the effect of coping style on the gray matter volume in patients with post-traumatic stress disorder (PTSD) who lost their only child, and the mediating role of gray matter volume in evaluating the influence of coping style in clinical symptoms of these parents.Methods:A total of 57 parents with PTSD (PTSD group) and 162 parents without PTSD (non-PTSD group) who lost their only child from September 2016 to March 2017 were enrolled from Jiangsu Province, China. Brain MRI data at resting state were collected. Voxel-based multiple regression analysis was performed to confirm the brain areas in which coping style main effect, diagnosis main effect and their interaction had significant influences in gray matter volumes. Correlations among gray matter volume of brain areas related to coping style, coping style scale scores, and clinician-administered PTSD scale (CAPS) scores were analyzed. Structural equation modeling was used to analyze the mediating role of gray matter volume in the influence of coping style in clinical symptoms of parents lost their only child.Results:(1) The coping style main effect did not significantly influence the gray matter volume in all subjects, and the diagnosis main effect had significant influence in gray matter volume in the right lingual gyrus; their interaction had significant influence in gray matter volume in the right peritalar fissure cortex and lingual gyrus. The positive coping style in the PTSD group had significant influence in the gray matter volumes of the right peritalar fissure cortex and lingual gyrus. (2) In the PTSD group, the scores of positive coping style were positively correlated with the gray matter volumes of the right talus fissure and the lingual gyrus ( P<0.05); the scores of positive coping style, and the gray matter volumes of the right talus fissure and the lingual gyrus were negatively correlated with scores of CAPS-C 5 and CAPS-C ( P<0.05). (3) In the PTSD group, positive coping style can positively predict the gray matter volumes of the right talus fissure and the lingual gyrus; the gray matter volumes of the right talus fissure and the lingual gyrus can negatively predict the avoidance-related symptoms. Conclusion:Positive coping style has influence in the gray matter volumes of the right talar fissure and lingual gyrus of PTSD patients lost their only child; and less positive coping style may affect the brain areas related to visual information processing, thus aggravating avoidance-related symptoms of PTSD patients.

Objective:To explore the incidence and risk factors of preoperative deep vein thrombosis (DVT) of elective total joint arthroplasty (TJA).Methods:Data of 500 patients before TJA from March 2015 to August 2016 who underwent ultrasound surveillance were retrospectively analyzed. All patients were divided into DVT group and non-DVT group according to results of ultrasound. Parameters including demographic data, basic medical history, and surgical information and laboratory indexes were collected. Risk factors were assessed via univariate, multivariate and logistic regression analysis.Results:Preoperative DVT was detected in 23 cases (4.6%, 23/500), all of which occurred in the intermuscular vein with no symptom, and among them there were 16 cases (5.6%, 16/285) before total knee arthroplasty and 7 cases (3.3%, 7/215) before total hip arthroplasty. Univariate analysis showed that age ( t=2.266, P=0.024), female patients ( χ2=4.028, P=0.045), history of hypertension ( χ2=7.907, P=0.005), D-dimer ≥0.5 μg/ml ( χ2=13.171, P < 0.001) were significantly higher than those in non-DVT group, and the differences were statistically significant. Multivariate analysis showed that D-dimer ≥0.5 μg/ml [ OR=6.655, 95% CI (1.929, 22.960), P=0.003] and history of hypertension [ OR=2.715, 95% CI (1.017, 7.250), P=0.046] were independent risk factors for preoperative DVT. Among them, the thrombus of 14 cases located in the operation side, 6 cases in non-operation side, and 3 cases in bilateral sides. Postoperative ultrasound showed that newly DVT occurred in 9 patients of whom 5 cases located in the contralateral muscular veins and 4 cases in the nearby muscular veins. After discharge, 22 patients (95.7%) with preoperative DVT were further evaluated by ultrasound. The average follow-up time was 3.0 months (range from 6 weeks to 9 months). The results showed that thrombus of 7 cases were completely dissolved, 13 cases were partially dissolved, and 2 cases remained unchanged. Thrombus extensions to proximal veins or symptomatic PE were not found. Conclusion:The incidence of preoperative DVT in patients with elective joint replacement was about 4.6%, among which D-dimer ≥0.5 μg/ml and history of hypertension were the risk factors for preoperative thrombosis.

Objective:To investigate the correlation between morphology of esophageal and gastric mucosal and Helicobacter pylori ( HP) infection under white light gastroscope. Methods:A retrospective analysis was performed on data of 1 339 patients who underwent 13C-urea breath test and white light gastroscopy at the same time in the Southwest Hospital of Army Medical University from September 2018 to August 2019. Chi-square test or Fisher exact probability method was used to analyze the difference on detection rates of 22 indexes of gastroscopic mucosal manifestation between the HP infection group ( n=422) and the non-infection group ( n=917). Then the indexes with difference were further analyzed by binary logistic regression. The receiver operating characteristic (ROC) curve was drawn, and the area under the curve and the sensitivity, specificity, positive predictive value and negative predictive value of prediction of HP infection was calculated. Results:The diffuse redness, spotted redness, mucosal swelling, enlarged folds, sticky mucus, digestive tract ulcer, nodularity, hyperplastic polyp, xanthoma, atrophy, intestinal metaplasia, and depressive erosion were more common in patients with HP infection (all P<0.05). Binary logistic regression analysis showed that diffuse redness ( P<0.001, OR=75.974, 95% CI: 32.551-177.327), spotted redness ( P=0.002, OR=3.360, 95% CI: 1.536-7.349), mucosal swelling ( P<0.001, OR=3.150, 95% CI: 1.654-5.996) were independent risk factors for HP infection. ROC curve analysis showed that the area under ROC curve of diffuse redness, spotted redness, mucosal swelling, enlarged folds, sticky mucus, peptic ulcer, and depressive erosion predicting HP infection were all greater than 0.5 ( P<0.05), among which, the area under curve of diffuse redness, spotted redness and mucosal swelling predicting HP infection were greater than 0.7. The sensitivities corresponding to the three indicators were 0.735, 0.512, and 0.445, the specificities were 0.992, 0.983, and 0.971, the positive predictive values were 0.978, 0.931, and 0.874, and the negative predictive values were 0.890, 0.814, and 0.792, respectively. Conclusion:Morphological manifestations of esophageal and gastric mucosa, especially diffuse redness, spotted redness, and mucosal swelling, are excellent indicators for HP infection under white light gastroscopy.